A pheromone-independent CarR protein controls carbapenem antibiotic synthesis in the opportunistic human pathogen Serratia marcescens.
Strain ATCC 39006 of Serratia marcescens makes the same carbapenem, (5R)-carbapen-2-em-3-carboxylic acid (Car), as the Erwinia carotovora strain GS101. Unlike E. carotovora, where the onset of production occurs in the late-exponential phase of growth in response to the accumulation of the small diffusible pheromone N-(3-oxohexanoyl)-L-homoserine lactone (OHHL), in S. marcescens carbapenem is produced throughout the growth phase and does not appear to involve any diffusible pheromone molecule. Two cosmids capable of restoring antibiotic production in E. carotovora group I carbapenem mutants were isolated from an S. marcescens gene library. These cosmids were shown to contain a homologue of the E. carotovora carR gene, encoding a CarR protein with homology to the LuxR family of transcriptional regulators. The S. marcescens carR was subcloned and shown to be capable of complementing in trans, in the absence of OHHL, an E. carotovora carR carI double mutant, releasing the heterologous E. carotovora host from pheromone dependence for carbapenem production. The apparent OHHL-independence of the S. marcescens CarR explains the constitutive nature of carbapenem production in this strain of S. marcescens.
Cox
A R J
ARJ
Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK.
Thomson
N R
NR
Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK.
Bycroft
B
B
Department of Pharmaceutical Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
Stewart
G S A B
GSAB
Department of Applied Biochemistry and Food Sciences, University of Nottingham Faculty of Agriculture and Food Sciences, Sutton Bonington LE12 5RD, UK.
Williams
P
P
Department of Pharmaceutical Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
Salmond
G P C
GPC
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015780:Carbapenems / Q000096:biosynthesis*; D003001:Cloning, Molecular; D003360:Cosmids; D004885:Erwinia / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D005816:Genetic Complementation Test; D006801:Humans; D008969:Molecular Sequence Data; D009894:Opportunistic Infections / Q000382:microbiology*; D010675:Pheromones / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012706:Serratia marcescens / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C091096:CarR protein, Azospirillum brasilense; D015780:Carbapenems; D010675:Pheromones; D011994:Recombinant Proteins